Heterocyclic compounds are regarded as one of the most important compounds in various fields, including material chemistry as well as biochemistry and pharmaceutical chemistry. Particularly, in the field of pharmaceutical chemistry, aromatic heterocyclic compounds have been used as key skeletons. Among such heterocyclic compounds, those having a 5,6-heteroaromatic cycle pattern are reported to provide biological activities, such as antibacterial, antiviral and anticancer activities. They are also reported to provide various pharmacological functions depending on the substitution pattern around an aromatic ring.
A cystic fibrosis conductance transmembrane regulator (CFTR) is a kind of carriers controlling the transport of anions, is expressed by various cell types including absorptive and secretory epithelial cells, and functions to control other ion channels and activity of protein as well as the flow of anions passing through a membrane. CTFR-mediated diseases include chronic obstructive pulmonary disease (COPD), dry eye syndrome or Sjogren's syndrome in addition to cystic fibrosis.
Vertex Pharmaceuticals, Inc. have reported modifiers for cystic fibrosis conductance transmembrane regulator having various structures through US Patent Application No. 2011-0257233, U.S. Pat. No. 7,999,113, U.S. Pat. No. 8,314,239, U.S. Pat. No. 8,410,321, U.S. Pat. No. 8,586,615, U.S. Pat. No. 8,614,325, or the like. However, the structures reported in the above patent documents are different from the structure of indolizino[3,2-c]quinoline.
Meanwhile, U.S. Pat. No. 5,155,255 discloses a method for preparing 8-methyl-7-(1-oxopropyl)indolizino[1,2-b]quinoline-9(11H)-one and International Patent Publication No. WO1992/007856 discloses the features of an indolizino[1,2-b]quinolinone compound, which merely shows pharmaceutical activity to viral infections due to the above-mentioned structural difference. Thus, there is no report about the compounds having an indolizino[3,2-c]quinoline skeleton disclosed herein.